The objective of the proposed research is to examine the relative contribution of tight junctions and pinocytotic vesicles in regulating the overall permeability of the pulmonary endothelium and epithelium to water-soluble molecules. To accomplish this the structure, patency and topographical location of tight junctions in pulmonary vascular endothelium and in airway and alveolar epithelium of adult and fetal rats will be examined, using enzymatic tracers, lanthanum staining and freeze fracture techniques. The number and distribution of pinocytotic vesicles in pulmonary endothelium and epithelium will be determined by morphometry, and the relative number of patent endothelial junctions calculated. To further determine the relative functional contribution that tight junctions and pinocytotic vesicles make to the overall permeability of the lung, two experimental models will be examined. In the first a new experimental model will be used to assess the role of serum proteins in the barrier function of tight junctions, and in the transport function of pinocytotic vesicles in the lung. Rats will have virtually their entire blood volume replaced by a fluorocarbon emulsion which is capable of performing the gas exchange function of hemoglobin. With prolonged exchange transfusion and serum protein removal, pulmonary edema can be induced without changing the oncotic pressure. In the second model, prolonged intravenous infusion of histamine will be used to increase the permeability of the alveolar capillary membrane to protein. In both these models the permeability of tight junctions will be assessed by means of enzymatic tracers and lanthanum staining, and the intrinsic structure of tight junctions examined by freeze fracture. The number of pinocytotic vesicles per unit volume of endothelium will be determined by morphometry, and the relative number of open endothelial junctions calculated.